Control and manipulation of charged particles in microfluidic systems is very useful for such applications as sample preconditioning (removal of interfering substances), electrophoretic separation (fractionation) of charged particles, enhanced or delayed mixing across a fluid interface, focusing particles in a fluid stream in one or two dimensions, and concentration of charged reactants at a fluid interface.
Microfluidic systems and methods of use have been described in detail (Verpoorte, E., Electrophoresis, 2002 23(5), 677–712; Lichtenberg, J., et al., Talanta, 2002.56(2), 233–266; Beebe, D. J., et al., Annual Review of Biomedical Engineering, 2002,4, 261–286; Wang, J., Electrophoresis, 2002, 23(5), 713–718; Becker, H. and L. E. Locascio, Talanta, 2002, 56(2), 267–287; Chovan, T. and A. Guttman, Trends in Biotechnology, 2002.20(3), 116–122; Becker, H. and C. Gartner, Electrophoresis, 2000, 21(1), 12–26; McDonald, J. C., et al., Electrophoresis, 2000, 21(1), 27–40; Weigl, B. H. and P. Yager, Science, 1999, 283(5400), 346–347; and Shoji, S., Microsystem Technology in Chemistry and Life Science, 1998, 163–188.) The behavior of fluids under laminar flow, a hallmark of microfluidic technologies, allows contacting of two miscible fluids in a microchannel such that mixing only occurs through diffusive transport, which may be augmented by an imposed field, as in the H-filter (Brody, J. P., et al., Biophys J 1996, 71, 3430–3441; Weigl, B. H., et al., Science 1999, 283, 346–347) and T-sensor (Kamholz, A. E., et al., Anal Chem 1999, 71, 5340–5347; Kamholz, A. E., et al., Biophys J 2001, 80, 155–160; Kamholz, A. E., et al., Biophys J 2001, 80, 1967–1972).
Methods for controlling the flow (transport) of particles in microfluidic systems have also been described, and include the use of electrophoresis, transverse electrophoresis, and hydrodynamic focusing, among others.
Flow cytometry, or the analysis of individual particles in a fluid, requires the single-file alignment of the particles in an analysis region. Flow cytometers in microfluidic systems rely on the use of sheath fluids to hydrodynamically focus particles in a stream.
Transverse electrophoresis requires the application of an external electric field across a microchannel to drive electrophoretic transport across the microchannel, and effectively separate charged species contained in the fluids in the microchannel. While effective, microfluidic electrophoresis adds complexity to the design of a microfluidic device by requiring additional fabrication techniques and steps for the incorporation of metal electrodes into the microfluidic channel. In addition, a microfluidic device incorporating traditional techniques of transverse electrophoresis requires an external voltage source.
The formation of an electrical potential at the interface of two fluids that have different ionic compositions, the liquid junction potential (LJP), is a phenomenon that has been well studied experimentally and theoretically since the late 1800's (MacInnes, D. A., The Principles of Electrochemistry, Reinhold Publishing, New York 1939; Planck, M., Ann. Phys. Chem. 1890, 40, 561–576; Jahn, H., Z. Phys. Chem. 1900, 33, 545–576; Henderson, P., Z. Phys. Chem. 1907, 59, 118–127; Henderson, P., Z. Phys. Chem. 1908, 63, 325–345; Lewis, G. N., Sargent, L. W., J. Am. Chem. Soc. 1909, 31, 363–367.; MacInnes, D. A., J. Am. Chem. Soc. 1915, 37, 2301–2307; Lamb, A. B., et al., J. Am. Chem. Soc. 1920, 42, 229–237; MacInnes, D. A., et al., J. Am. Chem. Soc. 1921, 43, 2563–2573; Harned, H. S., J. Phys. Chem. 1926, 30, 433–456; Roberts, E. J., et al., J. Am. Chem. Soc. 1927, 49, 2787–2791; Taylor, P. B., J. Phys. Chem. 1927, 31, 1478–1500; Guggenheim, E. A., J. Phys. Chem. 1929, 33, 842–849; Guggenheim, E. A., J. Am. Chem. Soc. 1930, 52, 1315–1337; Christiansen, T. F., IEEE Trans. Biomed. Eng. 1986, 33, 79–82; Forland, K. S., et al., J. Stat. Phys. 1995, 78, 513–529.) Methods of predicting the magnitude of the liquid junction potential as well as ways to compensate for it have been developed (MacInnes, 1939; MacInnes, 1921; Guggenheim, 1929; Guggenheim, 1930; Cobben, P. L. et al., Anal Chim Acta 1993, 276, 347–352; Lvov, S. N., et al., J Electroanal Chem 1996, 403, 25–30; Borge, G., et al., J Electroanal Chem 1997, 440,183–192). Detailed mathematical analysis and modeling of the underlying phenomena have also been pursued (Henry, J., et al., Asymptotic Anal 1995, 10, 279–302; Skryll, Yu., PCCP Phys Chem Chem Phys 2000, 2, 2969–2976; Samson, E., et al., J Colloid Interface Sci 1999, 215, 1–8). When an electrolyte, or ion concentration gradient exists between fluids flowing in adjacent laminar flow in a microfluidic channel, differential rates of diffusion of the ionic species can lead to a microscopic separation of charge, generating an electric potential. This potential is referred to as the liquid junction potential. This effect has been studied extensively in the presence of a selective barrier between two fluid phases, which often serves to accentuate the differences in transport of the chemical species. Although its effects often go overlooked (Demas, J. N., et al., Appl Spectrosc 1998, 52, 755–762; Greenlee, R. D., et al., Biotechnol Prog 1998,14, 300–309), the LJP could cause significant problems in many microfluidic systems by inducing spurious electrophoretic transport of analytes.
Borge (Borge, G., et al., J Electroanal Chem 1997, 440,183–192) discloses the use of LJP for the potentiometric measurement of equilibrium constants of systems displaying acid/base equilibrium. Beyond this application, the LJP has not to date been exploited as a tool due to its relatively low magnitude and the short distances over which it acts.
All references cited herein are incorporated in their entirety to the extent not inconsistent herewith.